ArticleMolecular and cellular biology1999
The E6 oncoproteins of high-risk papillomaviruses bind to a novel putative GAP protein, E6TP1, and target it for degradation.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
73 citing papers in PubMed, 188 citations in OpenAlex.
- Molecular Mechanisms Associated with the Development of the Metritis Complex in Dairy Cattle.Genes · 2024Article
- Ecdysoneless Protein Regulates Viral and Cellular mRNA Splicing to Promote Cervical Oncogenesis.Molecular cancer research : MCR · 2022Article
- The human papillomavirus oncoproteins: a review of the host pathways targeted on the road to transformation.The Journal of general virology · 2021Review
- Article
- Mammalian ECD Protein Is a Novel Negative Regulator of the PERK Arm of the Unfolded Protein Response.Molecular and cellular biology · 2017Article
- Roles of Rap1 signaling in tumor cell migration and invasion.Cancer biology & medicine · 2017Article
- Comparative expression study of sipa family members during early Xenopus laevis development.Development genes and evolution · 2016Article
- HPV16 E6 upregulates Aurora A expression.Oncology letters · 2016Article
- Sipa1l1 is an early biomarker of liver fibrosis in CCl4-treated rats.Biology open · 2016Article
- Testing for Ancient Selection Using Cross-population Allele Frequency Differentiation.Genetics · 2016Article
- Amnion as a surrogate tissue reporter of the effects of maternal preeclampsia on the fetus.Clinical epigenetics · 2016Article
- Viral Mimicry to Usurp Ubiquitin and SUMO Host Pathways.Viruses · 2015Review
- Article
- Oncogenes and RNA splicing of human tumor viruses.Emerging microbes & infections · 2014Review
- Papillomavirus E6 oncoproteins.Virology · 2013Review
- Research resource: identification of novel coregulators specific for thyroid hormone receptor-β2.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Cellular transformation by human papillomaviruses: lessons learned by comparing high- and low-risk viruses.Virology · 2012Review
- Histone deacetylase inhibitors upregulate Rap1GAP and inhibit Rap activity in thyroid tumor cells.Endocrine-related cancer · 2011Article
- Breast cancer subtypes: two decades of journey from cell culture to patients.Advances in experimental medicine and biology · 2011Review
- Viral oncogenes, noncoding RNAs, and RNA splicing in human tumor viruses.International journal of biological sciences · 2010Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The high-risk human papillomaviruses (HPVs) are associated with carcinomas of the cervix and other genital tumors. Previous studies have identified two viral oncoproteins, E6 and E7, which are expressed in the majority of HPV-associated carcinomas. The ability of high-risk HPV E6 protein to immortalize human mammary epithelial cells (MECs) has provided a single-gene model to study the mechanisms of E6-induced oncogenic transformation. In this system, the E6 protein targets the p53 tumor suppressor protein for degradation, and mutational analyses have shown that E6-induced degradation of p53 protein is required for MEC immortalization. However, the inability of most dominant-negative p53 mutants to induce efficient immortalization of MECs suggests the existence of additional targets of the HPV E6 oncoprotein. Using the yeast two-hybrid system, we have isolated a novel E6-binding protein. This polypeptide, designated E6TP1 (E6-targeted protein 1), exhibits high homology to GTPase-activating proteins for Rap, including SPA-1, tuberin, and Rap1GAP. The mRNA for E6TP1 is widely expressed in tissues and in vitro-cultured cell lines. The gene for E6TP1 localizes to chromosome 14q23.2-14q24.3 within a locus that has been shown to undergo loss of heterozygosity in malignant meningiomas. Importantly, E6TP1 is targeted for degradation by the high-risk but not the low-risk HPV E6 proteins both in vitro and in vivo. Furthermore, the immortalization-competent but not the immortalization-incompetent HPV16 E6 mutants target the E6TP1 protein for degradation. Our results identify a novel target for the E6 oncoprotein and provide a potential link between HPV E6 oncogenesis and alteration of a small G protein signaling pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.